The present invention relates to a novel bisphosphine compound having a chiral center on the phosphorus atom, which is useful as a ligand for asymmetric catalysts for use in asymmetric hydrogenation, and a process for the production of this bisphosphine compound, and further to a transition metal complex having this bisphosphine compound as a ligand, and a process for the asymmetric hydrogenation of an unsaturated carboxylic acid and its ester using this transition metal complex as an asymmetric catalyst for asymmetric hydrogenation.
Asymmetric catalytic synthesis is of great importance as the method for producing optically active fine chemicals that include agricultural products, pharmaceutical preparations and so on. An optically active phosphine ligand has played a major role as the ligand for transition metal complexes, and hence, a wide variety of related ligands have been reported to date. They are disclosed, for instance, in xe2x80x9cAsymmetric Synthesisxe2x80x9d, Vol. 5, authored by J. D. Morrison (published in 1985 by Academic Press Inc.), xe2x80x9cFundamentals and Applications of Chiral Technologyxe2x80x9d authored by Kazuo Achinami (published in 1999 by IBC) and xe2x80x9cAsymmetric Catalysis in Organic Synthesisxe2x80x9d authored by Ryoji Noyori.
Heretofore, compounds capable of causing a substituent such as a phenyl group existing on the phosphorus atom to be nonequivalent by C-chirality or axial asymmetry have been positively studied because they are obtainable by simple synthesis. It has been reported, however, that phosphine compounds having a chiral center directly on the phosphorus atom exert the most outstanding capability to develop asymmetry. Of these ligands, 1,2-bis(o-methoxyphenyl)phenylphosphino)ethane (generally called DIPAMP) is known which is a ligand having been studied in the earliest stage (U.S. Pat. No. 4,008,281 and Japanese Unexamined Patent Application Publication No. 50-113489). Furthermore, a new bisphosphine ligand structured to have a 1,2-bis(phosphino)-ethane group has been proposed by Imamoto et al. (J. Am. Chem. Soc., 1998, 120, pp. 1635-1636 and Japanese Unexamined Patent Application Publication No. 11-80179).
Thus, the 1,2-bis(phosphino)ethane-structured bisphosphine is known to be important as a chiral ligand. For an asymmetric reaction to progress with high reactivity, a substituent-containing aromatic group or a bulky alkyl group needs to be essentially existent on the chiral center, i.e., on the phosphorus atom. The bulky alkyl group known to be possibly attached to the P atom of such a 1,2-bis(phosphine)ethane structure, however, is limited only to a lower alkyl group such as 1,1-diethylpropyl or t-butyl, and a cycloalkyl group such as cyclopentyl, cyclohexyl or 1-adamantyl. Also in the case of other bisphosphine ligands, it is art-recognized that as the bulky alkyl group to be attached to the chiral center, that is, to the phosphorus atom, a chain alkyl group is usually used which has 2 to 4 carbon atoms and is typified by a t-butyl group and that as the alkyl group having a much larger number of carbon atoms, a cycloalkyl group is usually used which is typified by a cyclopentyl or cyclohexyl group. With regard to the chain alkyl group, a bulky alkyl group having 8 or more carbon atoms stands wholly unknown. Therefore, the 1,1,3,3-tetramethylbutyl group-containing bisphosphine compound according to the present invention can be said to be absolutely novel as far as the present inventors know.
The method disclosed in Japanese Unexamined Patent Application Publication No. 11-80179 involves stereoselective deprotonation of (xe2x88x92)-sparteine in an equimolar amount with S-butylithium at a cryogenic temperature of xe2x88x9278xc2x0 C., thereby obtaining an optically active bisphosphine-borane complex. Such a cryogenic temperature, however, is generally extremely difficult to carry out industrially and hence is far from being practically applicable. In addition, the S-butylithium is a compound that is vigorously active with respect to oxygen and moisture in the air and is difficult to handle on an industrial scale. As a further problem, an optically active form that can be obtained is limited only to a (S, S) form as an absolute configuration, and therefore, this is less advantageous to industrialization.
Optically active bisphosphine ligands have been thus far developed as mentioned above, but they cannot be said to be sufficient in respect of selectivity, catalytic activity and so on. Providing a phosphine ligand not yet known is crucial when the substrates, asymmetry conditions and the like are considered.
To settle the above-noted problems, the present inventors have conducted extensive research, finding that a transition metal complex having a novel 1,1,3,3-tetramethylbutyl group-containing bisphosphine compound as a ligand exhibits a high asymmetric catalytic activity, which group is a bulky substituent having 8 carbon atoms and represented by the foregoing general formula (1), and can also give both (S, S) and (R, R) forms as absolute configurations. This finding has led to completion of the present invention.
Namely, the objects of the invention are to provide a novel bisphosphine compound that is useful as a ligand capable of yielding a higher asymmetric catalytic activity than conventional catalysts, a process for producing the above bisphosphine compound, a transition metal complex having as a ligand the above bisphosphine compound capable of yielding a higher asymmetric catalytic activity than conventional catalysts, and a process for asymmetrically hydrogenating an unsaturated carboxylic acid and its ester using the above transition metal complex as a catalyst.
The novel bisphosphine compound intended to be provided by the present invention is a 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)-phosphino)ethane represented by the following general formula (1): 
(where txe2x80x94C8H17 denotes 1,1,3,3-tetramethylbutyl).
Moreover, the process for producing the above-mentioned bisphosphine compound comprises the steps of subjecting a phosphine oxide carboxylate represented by the following general formula (2): 
(where A1 and A2 denote a methyl group and a 1,1,3,3-tetramethyl-butyl group, respectively, and A1 and A2 denote their respective different groups) to Kolbe""s electrolytic coupling reaction, thereby obtaining 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphinoyl)-ethane represented by the following general formula (3): 
(where A1 and A2 have the same meanings as defined above, and A1 and A2 denote their respective different groups), and then reducing the resultant 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphinoyl)-ethane with a reducing agent.
Furthermore, the use of the above-mentioned bisphosphine compound is implemented in such a manner that a transition metal complex composed of the bisphosphine compound as a ligand is used as a catalyst to asymmetrically hydrogenate an unsaturated carboxylic acid and its ester.
The present invention will now be described in detail.
In the 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphino)-ethane of the invention represented by the foregoing general formula (1), a racemic form and an optically active form are included. As the optically active form, (S, S), (R, R) and meso forms exist, but the invention embraces all such forms.
Next, the process is described for the production of the optically active 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)-phosphino)ethane of the invention represented by the foregoing general formula (1).
The 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphino)-ethane of the invention represented by the foregoing general formula (1) can be easily produced, in essence, by performing a first step in which a phosphine oxide carboxylate represented by the foregoing general formula (2) is subjected to Kolbe""s electrolytic coupling reaction, whereby 1,2-bis(methyl-(1,1,3,3-tetramethyl-butyl)phosphinoyl)ethane represented by the foregoing general formula (3) is obtained, and then a first step in which the resultant 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphinoyl)-ethane is reduced with a reducing agent.
 less than First Step greater than 
The first step permits a phosphine oxide carboxylate of the foregoing general formula (2) to undergo Kolbe""s electrolytic coupling reaction, thereby obtaining 1,2-bis(methyl(1,1,3,3-tetra-methylbutyl)phosphinoyl)ethane of the foregoing general formula (3).
In the foregoing general formula (2) representing the reactant material, i.e., the phosphine oxide carboxylate, A1 and A2 denote a methyl group and a 1,1,3,3-tetramethylbutyl group, respectively, and A1 and A2denote their respective different groups.
Kolbe"" electrolytic coupling reaction can be effected in accordance with the method previously proposed by the present inventors in Japanese Unexamined Patent Application Publication No. 11-228586. Specifically, this reaction employs a solvent in accomplishing electrolysis, which solvent includes methanol and hydrous methanol. When the hydrous methanol is used, the water content is preferably not more than 4%. Aqueous solution or aprotic polar solvent such as acetonitrile is not very desirable since the starting material is likely to give a by-product derived abnormally by Kolbe""s reaction, such as olefin or alcohol (Hofer-Moest Reaction).
The pH of the electrolytic liquid is preferably neutral or acidulous. A support salt may be added, where desired, in stabilizing power distribution. Suitable support salts include sodium salts such as sodium perchlorate, sodium methylate and so on, and lithium salts such as lithium perchlorate and so on. Desirably, however, the use of a support salt should be avoided because the yield of the intended bisphosphine oxide decreases with increases in the amount of the salt. If such a support salt is anyway used, the amount of the salt to be added is preferably below 5 wt % based on 1 part by weight of the starting material.
As the electrode to be used, a platinum electrode is preferred to increase the concentration of radicals to be generated per unit area so that electrolysis can be effected at a high current density (at a high potential). An electrode made by plating platinum on a titanium plate can also be employed on an industrial scale. An electrode made of iridium, gold, palladium, lead dioxide or the like may be used in place of the platinum electrode. Preferably, the electrolytic liquid is maintained at a constant temperature by being immersed in a water bath. This is because the liquid temperature rises as the electrolysis volume increases. The electrolysis temperature is preferably relatively low, and the range of 0 to 20xc2x0 C. is particularly desirable. Moreover, the electrolytic liquid is preferably stirred to maintain its temperature uniform.
The electrolysis is performed usually by constant-current, electrolysis, and the current capacity is in the range of 0.1 to 3 A, preferably 0.5 to 2 A. The electrode-to-electrode distance is usually in the range of about 1 to 5 mm to ensure that the current density be in the range of 10 to 100 mA/cm2. The current distribution time is variable with the starting material and electrolysis conditions used, but is usually in the range of 0.5 to 36 hours, preferably about 1 to 10 hours.
Upon completion of the reaction, the solvent is removed by distillation to give a 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)-phosphinoyl)ethane represented by the foregoing general formula (3). In the present invention, the resultant compound can be purified by conventional means such as recrystallization and so on.
According to the present invention, an optically active form of the 1,2-bis(methyl(1,1,3,3-tetramethybutyl)phosphino)-ethane of the foregoing general formula (1) can be easily produced, with axial asymmetry held on the P atom, by subjecting a reactant material, i.e., a phosphine oxide carboxylate of the foregoing general formula (2), to Kolbe""s electrolytic coupling reaction stated earlier, wherein the reactant material has been optically resolved in advance, and subsequently by carrying out a second step that will be described later.
No particular restriction is imposed on the method for the optical resolution of the phosphine oxide carboxylate of the foregoing general formula (2). As one example, a method proposed previously by the present inventors is suitably useful in which a racemic mixture of the phosphine oxide carboxylate of the foregoing general formula (2) is treated with an optically active amine such as 1-phenylethylamine to form a diastereoisomer salt which is then resolved by utilizing the solubility difference with respect to a solvent used (Japanese Unexamined Patent Application Publication No. 10-29803).
 less than Second Step greater than 
The second step permits the 1,2-bis(methyl(1,1,3,3-tetra-methylbutyl)phosphinoyl)ethane of the foregoing general formula (3), which has been obtained as mentioned above, to be reduced with a reducing agent, thereby obtaining the intended 1,2-bis(methyl-(1,1,3,3-tetramethylbutyl)phosphino)ethane of the foregoing general formula (1).
The reducing agent for use in reducing the 1,2-bis(methyl-(1,1,3,3-tetramethylbutyl)phosphinoyl)ethane of the foregoing general formula (3) is not particularly restricted, but a silane compound may be generally employed. The silane compound includes, for example, trichlorosilane, dichlorosilane, methyl-dichlorosilane, dimethylchlorosilane, phenyldichlorosilane, phenylmethylchloro-silane, diphenylchlorosilane, phenylsilane and so on. Of these compounds, phenylsilane is preferred.
The amount of the reducing agent to be added is usually in the range of 1 to 100 mol, preferably 5 to 50 mol, based on 1 mol of the 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphinoyl)ethane of the foregoing general formula (3). The reaction temperature is usually in the range of room temperature to 150xc2x0 C., preferably 50 to 120xc2x0 C., whereas the reaction time is usually in the range of 1 to 48, preferably 5 to 24 hours.
In this way, the 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)-phosphino)ethane of the foregoing general formula (1) is obtained in a racemic or optically active form. The optically active form depends on the (S) and (R) forms of the starting material, i.e., the phosphine oxide carboxylate of the foregoing general formula (2). When the above-described first and second steps are carried out using a desired form of starting material, the 1,2-bis(methyl-(1,1,3,3-tetramethylbutyl)phosphino)ethane of the foregoing general formula (1) can be synthesized in an optically active form chosen arbitrarily from (S, S), (R, R) and meso forms.
The 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphino)-ethane of the foregoing general formula (1) according to the present invention can cooperate as a ligand with a transition metal in forming the corresponding complex. The transition metal that can form a complex includes, for example, rhodium, ruthenium, iridium, palladium, nickel and so on. A rhodium metal is preferable.
In the formulae of transition metal complexes that will follow, cod denotes 1,5-cyclooctadiene, nbd denotes norbornadiene, Ph denotes phenyl, and Ac denotes acetyl, respectively, while L denotes the optically active 1,2-bis(methyl(1,1,3,3-tetramethyl-butyl)phosphino)ethane of the foregoing general formula (1).
 less than Rhodium Complex greater than 
As the method of forming a complex using a rhodium metal together with the optically active 1,2-bis(methyl(1,1,3,3-tetra-methylbutyl)phosphino)ethane of the foregoing general formula (1) as a ligand, the optically active 1,2-bis(methyl(1,1,3,3-tetramethyl-butyl)-phosphino)ethane of the foregoing general formula (1) according to the present invention may be reacted, for example, with a bis-(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate salt by a method disclosed, for example, in Courses in Experimental Chemistry, 4th Edition (edited by the Chemical Society of Japan, published by Maruzen Co., Ltd., Vol. 18, pp. 327-353).
Specific examples of the resulting compounds are enumerated below.
Rh(CO)(acac)(L), [Rh(cod)(L)]ClO4, [Rh(cod)(L)]PF6, [Rh(cod)-(L)]BF4, [Rh(nbd)(L)]ClP4, [Rh(nbd)(L)]PF6, [Rh(nbd)(L)]BF4, Rh(cod)(L)Cl, Rh(nbd)(L)Cl, Rh(cod)(L)Br and Rh(nbd)(L)Br.
 less than Palladium Complex greater than 
A palladium complex can be prepared by a method disclosed by Uozumi and Hayashi (Y. Uozumi and T. Hayashi, J. Am. Chem. Soc., 1991, 113, 9887), wherein L is reacted, for example, with xcfx80-allylpalladium chloride. Specific examples of the resulting compound are enumerated below.
PdCl2(L), (xcfx80-allyl)Pd(L), [Pd(L)]ClO4, [Pd(L)]PF6 and [Pd(L)]BF4.
 less than Ruthenium Complex greater than 
A ruthenium complex can be prepared by a method disclosed by Mashima et al. (K. Mashima, K. Kusano, T. Ohta, R. Noyori and H. Takaya, J. Chem. Soc., Chem. Commun., 1208 (1989)), wherein L and, for example, [Ru(p-cymene)I2]2 are stirred with heating in methylene chloride and ethanol. Specific examples of the resulting compounds are enumerated below.
[RuCl(benzene)(L)]Cl, [RuBr(benzene(L)]Br, [RuI(benzene)-(L)]I, [RuCl(p-cymene)(L)]Cl, [RuBr(p-cymene)(L)]Br, [RuI(p-cymene)(L)]I, [RuCl(mesitylene)(L)]Cl, [RuBr(mesitylene)(L)]Br, [RuI(mesitylene)(L)]I, [RuCl(hexamethylbenzene)(L)]Cl, [RuBr(hexamethylbenzene)(L)]Br and [RuL(hexamethylbenzene)-(L)]I.
 less than Iridium Complex greater than 
An iridium complex can be prepared by a method disclosed by Mashima et al. (K. Mashima, T. Akutagawa, X. Zhang, T. Taketomi and H. Kumobayashi, J. Organomet. Chem., 1992, 428, 213), wherein L is reacted, for example, with [Ir(cod)(CH3CN)2]BF4 with stirring in tetrahydrofuran. Specific examples of the resulting compounds are enumerated below.
[Ir(cod)(L)]ClO4, [Ir(cod)(L)]PF6, [Ir(cod)(L)]BF4, [Ir(nbd)-(L)]ClO4, [Ir(nbd)(L)]PF6, [Ir(nbd)(L)]BF4, Ir(cod)(L)Cl, Ir(nbd)(L)Cl, Ir(cod)(L)Br and Ir(nbd)(L)Br.
The transition metal complex, preferably the rhodium metal complex, derived from the optically active 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphino)ethane of the foregoing general formula (1) according to the present invention and a transition metal compound can be utilized as a catalyst for asymmetric synthesis.
Next, asymmetric hydrogenation is described which uses the transition metal complex of the present invention.
An unsaturated carboxylic acid of the following general formula (4): 
or its ester is asymmetrically hydrogenated using the transition metal complex of the invention as a catalyst, whereby a saturated carboxylic acid of the following general formula (5): 
or its ester is obtained. The step for doing so can be performed in a conventional fashion. Namely, the unsaturated carboxylic acid of the foregoing general formula (4) or its ester is placed, together with the transition metal complex catalyst of the invention, in a pressure tight case under a nitrogen atmosphere, and reaction is effected with hydrogen gas filled.
In the foregoing general formulas (4) and (5), R1, R2 and R3 denote a hydrogen atom, a straight- or branched-alkyl, aryl or aralkyl group, and R4 denotes a straight- or branched-alkyl, aryl, aralkyl, xe2x80x94CH2COOR5 group (where R5 denotes a straight- or branched-alkyl, aryl or aralkyl group) or xe2x80x94NHR6 group (where R6 denotes a formyl, straight- or branched-alkyl, aryl or aralkyl group).
Examples of the alkyl group defined in R1 to R6 are methyl, ethyl, propyl, isopropyl, butyl, octyl, decyl, and so on of C1 to C10. Examples of the aryl group are phenyl, naphthyl and so on of C6 to C12, and examples of the aralkyl group are benzyl, phenethyl, naphtylmethyl and so on. The alkyl, aryl, and aralkyl groups noted here may have substituents, which are inert to hydrogenation, such as alkyl, halogen, alkoxy and ester.
The amount of the transition metal complex of the present invention to be used as a catalyst is usually in the range of 0.02 to 0.00001 mol, preferably 0.005 to 0.0001 mol, based on 1 mol of the carboxylic acid of the foregoing general formula (4) or its ester. The solvent is not particularly restricted on condition that it is inert to the reactant material used and reaction product obtained. For example, alcohols, such as methanol, ethanol, isopropyl alcohol and the like, THF, benzene, toluene and so on can be used alone or as a mixed solvent. The amount of the solvent to be used is usually in the range of 0.5 to 200 mol, preferably 5 to 100 mol, based on 1 mol of the unsaturated carboxylic acid of the foregoing general formula (3) or its ester. The hydrogen gas pressure can be in the range of 0.1 to 100 atm, but is preferably in the range of 0.1 to 5 atm. This is because as the gas pressure becomes higher, asymmetric hydrogenation generally tends to be less selective, eventually causing a decline in asymmetry yield. The reaction temperature is in the range of 0 to 100xc2x0 C., preferably 20 to 50xc2x0 C.
With regard to the absolute configuration of the optically active 1,2-bis(methyl(1,1,3,3-tetramethylbutyl)phosphino)ethane of the foregoing general formula (1) according to the present invention, both forms of (R, R) and (S, S) are achieved. Hence, a specific target having a desired absolute configuration can be obtained with high optical purity and also with good yield using a transition metal complex as a catalyst, which complex has as a ligand either one selected from the (R, R) and (S, S) forms of the above bisphosphine.